# Transcriptome profiling of macrophages persistently infected with human respiratory syncytial virus and effect of recombinant Taenia solium calreticulin on immune-related genes

## TL;DR

This study explores how human respiratory syncytial virus (hRSV) affects macrophage gene expression and how a protein from a tapeworm can reduce viral load and boost immune responses.

## Contribution

The study reveals a transcriptional signature of hRSV persistence in macrophages and shows that recombinant Taenia solium calreticulin can reverse some of these effects.

## Key findings

- hRSV persistence alters antiviral, inflammatory, and metabolic gene expression in macrophages.
- rTsCRT increases proinflammatory cytokines and reduces hRSV genome copies in infected macrophages.
- Persistent macrophages remain responsive to external stimuli, suggesting reversibility of viral persistence effects.

## Abstract

Human respiratory syncytial virus (hRSV) is a main cause of bronchiolitis in infants and its persistence has been described in immunocompromised subjects. However, limited evidence has been reported on the gene expression triggered by the hRSV and the effect of recombinant Taenia solium-derived calreticulin (rTsCRT).

Using a comprehensive microarray approach, we analyzed the transcriptome profile of a macrophage cell line that has supported hRSV persistence for over 150 passages. We compared the gene expression of persistently infected and non-infected macrophages. We also evaluated the effect of rTsCRT on hRSV-infected macrophage gene transcription, as well as on cytokine production and number of copies of the persistent hRSV genome.

Our analysis showed that hRSV long-term virus infection significantly alters mRNA expression of antiviral, inflammatory, as well as arginine and lipid metabolism-associated genes, revealing a transcriptional signature that suggests a mixed M1/M2 phenotype. The resulting host-virus equilibrium allows for the regulation of viral replication, while evading the antiviral and proinflammatory responses. Interestingly, rTsCRT stimulus upregulated Tnfα, Il6 and Nos2 mRNA. We found increased levels of both proinflammatory cytokines and nitrite levels in the conditioned media of persistent macrophages treated with rTsCRT. This increase was associated with a significant reduction in viral genome copies.

hRSV persistently infected macrophages retain responsiveness to external stimuli and demonstrate that the profound changes induced by viral persistence are potentially reversible. Our observations contribute to the understanding of the mechanisms related to hRSV persistence in macrophages and have implications for the development of targeted therapies to eliminate persistent infections or reduce the negative effects related with chronic inflammatory diseases associated with hRSV infection.